The overall goal described in this grant proposal is to measure the efficacy of the ORI 1146 as an anti-cancer chemotherapeutic on two human xenografts in nude mice. ORI 1146 is cytotoxic to a number of different cell lines with low IC50 values and display a G2/M cell cycle arrest. OR 1146 is a number of different cell lines with low IC50 values and display a G2/M cell cycle arrest. ORI 1146 is a unique polyamine analog. Antimitotic activity was a surprising and novel observation for compounds of this class. We believe that this represents an opportunity for the development of an antimitotic agent that will not have the usual multidrug resistance mechanisms. It is also likely to not have overlapping side effects and toxicities with standard cytotoxics. If efficacy is shown for this compound, Phase II will be the preparation for an IND submission. This will include GMP manufacturing, additional efficacy trials, GLP toxicity trials, safety pharmacology testing and clinical plan development. The Phase III of product development is the clinical trial portion. It would be our intention that this phase would be done in collaboration with a larger pharmaceutical corporation. PROPOSED COMMERCIAL APPLICATION: Antimitotic cancer chemotherapeutics currently represent a multi-billion dollar market. The potential product is an antimitotic agent that would not suffer from the common multi-drug resistance mechanisms of the current drugs.